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PubMedDate not supplied

Surgical strategies for differentiated carcinoma of the thyroid isthmus.

The postoperative outcome (including clinicopathologic features) in 19 patients with differentiated thyroid cancer of the isthmus was investigated to develop more appropriate surgical strategies for these lesions. The extent of thyroidectomy, including neck dissection, tumor size, nodal involvement, and other clinical features were evaluated. The incidence of intraglandular dissemination was about 16% in all patients. Analysis of regional node metastatic distribution revealed no definite metastatic pattern. In addition, there was no apparent correlation between tumor size and nodal involvement. Two of the six patients who underwent total thyroidectomy suffered permanent postoperative hypoparathyroidism. It is thus recommended that isthmusectomy, including an adequate edge of surrounding normal thyroid tissues of each lobe and modified or limited neck dissection when cervical nodes are palpably enlarged, is sufficient as an appropriate primary surgical procedure for differentiated carcinoma of the thyroid isthmus.

Adenocarcinoma↗

PubMed2002

Extracellular matrix building marked by the N-terminal propeptide of procollagen type I reflect aggressiveness of recurrent breast cancer.

The purpose of our study was to examine the association between extracellular matrix homeostasis and aggressive breast cancer as reflected by the synthesis of type I collagen marked by circulating concentration of the aminoterminal propeptide of type I procollagen (PINP). Pre-therapeutic serum PINP concentrations were measured in 154 healthy women and 100 patients referred with their first metastatic manifestation of breast cancer and correlated to the metastatic pattern, response to therapy, time to progression and survival with a minimal follow-up of 5 years. Fifty-four percent of the patients had serum PINP concentrations greater than the 95th percentile of the healthy controls and 38% were high PINP level patients with values clearly outside normal range (>125 ng/ml). Patients with high PINP levels were more sick (p = 0.002), had a higher tumor burden (p = 0.013) and revealed a lower responsiveness to anthracycline-based therapy (p = 0.0002) as well as an accelerated time to disease progression (p = 0.00001) and death (p = 0.0006). Median survival in the high serum PINP level group was less than half of that in the group with low PINP level (14.5 vs. 32 months). The lowest PINP levels were seen when the cancer was restricted to the lymph node and skin and increasing PINP levels were found if the cancer had spread to the lungs, the bones, the bone marrow and the liver. High PINP level at recurrence and lack of estrogen receptors (ER) independently reflected aggressive tumor behavior after recurrence with an equal great impact on time to progression and survival. Patients with a high PINP level and primarily ER-negative tumors survived a median of only 6 months with no one alive after 22 months. By contrast patients with a low PINP level and ER-positive tumors had a median survival of 37 months and 23% were still alive after 5 years. Aggressive breast cancer induces a strong fibroproliferative response with synthesis of type I collagen. Serum PINP levels may be a diagnostic and prognostic tool that indicate breast cancer activity, aggressiveness, expansion and metastasis and a predictor of outcome after anthracycline-based chemotherapy.

Adult↗

PubMed1992

Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes.

Four murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v-Ha-ras, SV40 large T and v-src, SV40 large T and neu, adenovirus EIA and v-Ha-ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except EIA-ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor-bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases.

Adenovirus Early Proteins↗

PubMed1995

Human peri-tumoral and lung fibroblasts produce paracrine motility factors for recently established human sarcoma cell strains.

Paracrine motogenic cytokines secreted by normal cells can stimulate metastatic cell invasion. For example, human fibroblasts secrete hepatocyte growth factor/scatter factor (HGF/SF), which stimulates paracrine migration of epithelial and certain carcinoma cells, and migration-stimulating factor (MSF), which stimulates autocrine migration of fibroblasts from certain breast carcinomas. We found that human peri-tumoral and lung fibroblasts secrete motility-stimulating activity for several recently established human sarcoma cell strains. Motility of lung metastasis-derived SYN-I sarcoma cells was preferentially stimulated by human lung and peri-tumoral fibroblast motility-stimulating factors (FMSFs). FMSFs were non-dialyzable, susceptible to trypsin and sensitive to dithiothreitol. Cycloheximide inhibited accumulation of FMSF activity in conditioned medium; however, addition of cycloheximide to the migration assay did not significantly affect motility-stimulating activity. Purified HGF/SF, rabbit anti-hHGF and RT-PCR analysis of peri-tumoral and lung fibroblast HGF/SF mRNA expression indicated that FMSF activity was unrelated to HGF/SF. Partial purification of FMSF by gel exclusion chromatography revealed several peaks of activity, suggesting multiple FMSF molecules or complexes. Since human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), FMSF may play a role in this process independent of HGF/SF.

Base Sequence↗

PubMed2004

The natural course of cutaneous melanoma.

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.

Humans↗

PubMed1986

Lung cancer in men aged 40 or younger.

Twenty-nine cases of lung cancer occurring in men aged 40 or less were examined at autopsy. Histologic types of cancer and metastatic patterns in this group of patients were similar to those seen in middle-aged or elderly patients except for a lower occurrence of lymphatic spread in the younger group.

Adult↗

PubMed1986

Pathogenesis and characteristics of spontaneously metastasizing mammary carcinomas and the general principle of metastasis.

Chemical mammary carcinogenesis in immunologically attennuated W/Fu female rats, subjected to specific and nonspecific immunostimulations, yielded many spontaneously metastasizing adenocarcinomas with varying degrees of glandular differentiation, and growth rates. The pathogenesis of these tumors suggested that while carcinogens transform target cells, the host immune system endows them with metastatic potential. The metastatic pathways were recognizable as hematogenous, lymphogenous, or hematogenous-lymphogenous combined, according to the capacity of the tumor cells to intravasate the lymphatic and/or vascular channel and traverse the pulmonary artery. The same metastatic pattern can be reproduced with cells from any of the organs involved, indicating that it is inherent in all cells within a given tumor, rather than being determined by the organs they colonize. The biological, biochemical and immunological characteristics of these tumors resemble human breast cancer thus becoming an effective tool in the formulation of the general principle of metastasis by malignant solid tumors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1989

Infiltrating lobular carcinoma of the breast treated with segmental and modified radical mastectomy.

Conservative treatment of infiltrating lobular carcinoma (ILC) has previously been examined only in terms of general breast carcinoma studies. However, this lesion has been shown to differ from the more common infiltrating ductal carcinoma (IDC) in estrogen receptor (ER) status, metastatic patterns, and bilaterality. Therefore, it is necessary for the physician to consider these distinctions when planning both pre- and post-operative treatment. To determine the effectiveness of both segmental and modified radical mastectomies, the medical records of 26 patients with ILC were reviewed, and follow-up information was obtained. In addition to surgical treatment, hormonal manipulation and/or radiotherapy were used when appropriate. We found the results of a conservative approach in the treatment of this disease to be comparable to the more radical procedures with respect to overall survival and disease-free intervals. The single factor that most affected a patient's prognosis was involvement of the axillary nodes.

Adult↗

PubMed1993

Carcinoembryonic antigen (CEA) in stage IV gastric cancer as a risk factor for liver metastasis: a univariate and multivariate analysis.

Serum carcinoembryonic antigen (CEA) levels were determined in 68 patients with Stage IV gastric cancers, the objective being to examine the clinicopathological relationship between the metastatic patterns of gastric cancer and the serum CEA level. Of the 68 patients, 31 were diagnosed as cases of liver metastases and 37 as cases of peritoneal dissemination. Serum CEA levels were elevated in 21 of 31 patients (67.8%) with liver metastases and in 7 of 37 patients (18.9%) with peritoneal dissemination (P < 0.01). A univariate analysis showed that liver metastasis correlated with a young age (P < 0.01), the lower portion of stomach (P < 0.05), Borrmann types 1 and 2 (P < 0.01), differentiated type (P < 0.01), and nonserosal involvement (P < 0.05) more than did peritoneal dissemination. A multivariate analysis showed that in addition to Borrmann type 1 and 2, elevated CEA levels (> 2.5 ng/ml) is an independent risk factor involved in liver metastasis. Thus careful follow-up and postoperative adjuvant therapy are required for patients with elevated CEA levels, even with "curative" resection.

Adult↗

PubMed1992

Metastasizing lung carcinomas in Hann: Wistar rats.

In Hann:Wistar rats, 25 weekly subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight induced lung carcinomas which metastasized partly. The incidence of the primaries was 2.5, 20.0, 77.5 and 100% in the males and 0, 0, 12.5 and 57.5% in the females, respectively. The frequency of metastases was 0, 12.5, 38.7 and 72.5% in the males and 0, 0, 40.0 and 52.2% in the females, respectively. The most common metastatic sites in males and females together were: lung-associated lymph nodes (82.1%), adrenal gland (53.6%), kidney (39.3%), pancreas (32.1%), bones (16.1%), heart (12.5%), mesentery (12.5%) and CNS (8.9%). In the females, metastases were also detected in the uterus (21.4%) and ovary (42.9%). The results indicate that: (1) through subcutaneous injections of DPNA metastasizing lung carcinomas can be induced with high incidence, and (2) the metastatic pattern is very similar to human cases. Thus, this model could be useful for the study of metastasizing lung carcinomas in experimental animals.

Adenocarcinoma↗

PubMed1986

Metastatic epidural osteosarcoma initially diagnosed as cisplatin neuropathy.

Unexpected early epidural spinal metastasis in a case of osteosarcoma occurred in a patient receiving treatment with cis-diamminedichloroplatinum-II (cisplatin). The initial neurologic symptomatology manifested as paresthesias in the feet which developed 2 months after initiation of treatment (cumulative dose of cisplatin 450 mg/M2) at which stage the primary tumor demonstrated a marked response. Concurrently two small pulmonary metastases appeared. Epidural metastasis in osteosarcoma is generally considered a late complication and is usually associated with disseminated disease. This communication draws attention to changes in the metastatic pattern which may occur with the administration of seemingly effective treatment and the potential for confusing the symptomatology of epidural spinal metastasis with cisplatin neuropathy.

Adolescent↗

PubMed1993

Intrahepatic distant metastasis and metachronous multicentric occurrence in solitary hepatocellular carcinoma of less than five centimeters in diameter.

During the 7 years from 1984 to 1990, 36 patients underwent liver resection for solitary hepatocellular carcinoma (HCC) measuring less than 5 cm in diameter, with no intrahepatic vascular invasion on imaging diagnoses and no macroscopic infiltration into the tumor capsule or surrounding tissues. Although HCC is less likely to cause intrahepatic adjacent metastasis to the cut liver surface, an analysis revealed the possibility of intrahepatic distant metastasis and metachronous multicentric occurrences, even after complete removal of the primary tumor. The 5-year cumulative survival rate was 53%, while the 5-year cumulative recurrence-free survival rate was 19%. Of the 36 patients, 18 (50%) had suffered a recurrence by April, 1992, one with extrahepatic metastasis. Recurrence of intrahepatic metastasis was multifocal in 5 patients, single and adjacent in 1, and single (or a few) and distant in 11. Multifocal recurrence was observed within 1 year after liver resection. The sole single and adjacent metastatic case occurred in one of eight patients in the recurrent group in whom distance of the surgical margin was less than 1 cm [TW(+)]. Multicentric occurrence was found in 6 of 13 patients (46%) whose recurrent tumors were examined histologically, and all belonged to the "single (or a few) and distant" type of recurrence. In this report, we also present two typical cases of metastasis, one being multifocal metastasis occurring within 3 months after liver resection and the other being intrahepatic metastasis occurring after a 4-year-dormant state, to demonstrate the complicated nature of the intrahepatic metastatic pattern.

Adult↗

PubMed1988

The influence of the microenvironment of liver-specific tumor cell colonization in a murine tumor model.

UNLABELLED: Malignant tumors often show an organ-specific metastatic spread. Some cells of the primary apparently bear an affinity for growing in the microenvironment of certain organs. After i.v. injection of myofibrosarcoma cells from the primary ER 15-P into the tail vein of male C57/Bl6J mice, metastases developed in various organs. A tumor cell line (ER 15-Me3) isolated from liver metastases of the primary was found to colonize preferentially to the liver. To find out whether the liver specificity of the tumor cell line ER 15-Me3 depended on the hepatic microenvironment, tumor cells from this line were transplanted i.m. into the thighs of mice once (ER 15-Me3 i.m.1) or 5 times (ER 15-Me3 i.m.5), and then injected into the tail vein of mice. A part of the 5-times passaged tumor cell line was also injected into the mesenteric vein (ER 15-Me3 i.m.5-Me1) prior to reinjection into the tail vein. RESULTS: After i.v. administration of tumor cells from the first i.m. passage of the tumor cell line (ER 15-Me3 i.m.1) into the tail vein, the liver-specific metastatic behavior of tumor cells remained stable. Following the i.v. injection of tumor cells from the 5th i.m. transplant generation of the tumor cell line (ER 15-Me3 i.m.5) into the tail vein, organ distribution was similar to that of the primary. After only 1 mesenteric vein passage of the 5-times i.m. transplanted line ER 15-Me3 i.m.5-Me1 followed by i.v. injection into the tail vein, did tumor cells regain their liver-specific colonizing potential. Thus, the liver-specific tumor cell line seems to contain a small number of other tumor cell populations from the unselected primary. In the muscle, these tumor cells have a growth advantage over the liver-specific cells, while the latter will grow better in the liver. This indicates that the microenvironment may be one important factor influencing the organ-specific metastatic pattern of tumor cells.

Animals↗

PubMed1990

Anticancer-agent-linked phosphonates with antiosteolytic and antineoplastic properties: a promising perspective in the treatment of bone-related malignancies?

Bisphosphonates are compounds with a high affinity for bone and other calcified tissues. They inhibit tumor-induced bone destruction and the associated hypercalcemia by hindering the activity of the osteoclasts. Owing to a long biological half-life of bisphosphonates in the bone, a treatment using a prophylactic regimen seems possible. This paper summarizes preclinical studies with the bisphosphonate 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid and two methyl derivatives; 3-N,N-dimethylamino-1-hydroxypropylidene-1,1-diphosphonic acid and 4-N,N-dimetyhlamino-1-hydroxybutylidene-1,1-diphosphonic acid with respect to their bone-protecting activity in therapy as well as in prophylaxis. To find substances that are useful for the treatment of primary tumor, as well as bone metastasis, we synthesized and tested cis-diammine[nitrilotris(methylphosphonato)(2-)-O1,N1]platin um(II) and cis-diammine[( bis-(phosphonatomethyl)amino]acetato(2-)-O1,N1)platinum(II), which contain both an osteotropic and an antineoplastic moiety. Experiments were carried out: (a) in the intratibial transplanted Walker carcinosarcoma 256B of the rat, which mimics osteolytic bone metastasis, and (b) in the transplantable osteosarcoma of the rat, which shows a histology and metastatic pattern similar to that found in man. These investigations indicate that it is possible to effect adjuvant therapy of bone metastases by combination of two compounds with different properties into one structure without losing the therapeutic characteristics of the parent compounds. They thus provide evidence that it may be possible to design compounds well suited for the therapeutic or prophylactic treatment of bone-related malignancies.

Animals↗

PubMed1994

The role of the spleen in the organ-specific metastasis of murine BW 5147 T lymphomas.

Organ-specific metastasis of tumour cells may result from selective invasion and growth or from selective host cell responses. The present study demonstrates how selective interactions with the host affect the metastatic pattern of two murine T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous inoculation into syngeneic mice BW-14 cells preferentially colonize the kidneys, whereas BW-19 cells metastasize mainly to the spleen and the liver. The organ-specific behaviour of the two cell lines appears to be determined by a differential interaction with the spleen microenvironment. Inoculation of BW-14 cells into splenectomized mice results in increased liver colonization, indicating a negative effect of the spleen on BW-14 tumour development in the liver. Macrophages are likely to be involved in this inhibition, since inoculation of BW-14 cells into macrophage-depleted mice also leads to increased liver and spleen metastasis. In contrast, inoculation of BW-19 cells into splenectomized mice results in decreased liver metastasis, which indicates that the spleen exerts a stimulating effect on BW-19 cells. Macrophages also appear to be involved in this stimulation, since macrophage depletion causes a similar decrease in liver and spleen colonization. Hence components of the splenic microenvironment, probably macrophages, exert inhibiting or stimulating activities on BW-14 or BW-19 cells respectively, thereby determining the subsequent liver or kidney colonization.

Animals↗

PubMed1996

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma.

The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( < or = 25% of stained cells) or high ( > 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3-58). Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( > or = 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analysis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.

Adult↗

PubMedDate not supplied

Therapeutic efficacy of two different cytostatic-linked phosphonates in combination with razoxane in the transplantable osteosarcoma of the rat.

Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1- hydroxybutane-1,1-bisphosphonic acid (BAD) and aminotris-(methylenephosphonato)-diamminoplatinum(II) (ADP) that both have cytostatic and osteotropic properties, have shown good therapeutic efficacy against an osteosarcoma which metastasizes and kills by lung metastases. We therefore combined each of these drugs with the antimetastic agent razoxane. Razoxane (20 mg/kg i.p., 5 days/week for 6 weeks) was administered in combination with either BAD (30 mg/kg i.p.) or ADP (37.5 mg/kg i.v.) twice weekly for 3 weeks. Tumour volumes, body weight, survival time and occurrence of metastases were recorded, in addition to the measurement of the metastasis area compared to the total lung area in serial histological lung samples. In both experiments, razoxane effected a significant increase in life span while being ineffective in tumour inhibition. Razoxane in combination with BAD displayed an enhanced anticancer activity which was not significant. ADP had a good antineoplastic activity and a large increase in survival time (144 per cent ILS). Razoxane used in combination with ADP did not influence antitumour efficacy. Median survivals of both ADP-treated groups were significantly longer than the razoxane-treated group. Analysis of the lung metastasis area showed a maximum of 57 per cent for the controls while all treated groups occupied a lesser area. The lowest metastases area was found with the combination treatment BAD + RAZ (18 per cent). This was considered an antimetastatic effect, while ADP treatment effected a time delay only. No change in metastatic pattern was observed in any of the treatment groups. Histological examination showed no effect on the capillaries in the proliferating region of the tumours that could account for the lower occurrence of metastases.

Animals↗

PubMed1993

Clear cell sarcoma of the kidney. A case report.

Clear cell sarcoma of the kidney, a tumor which can resemble Wilms' tumor on imaging studies, possesses a much worse prognosis because of its skeletal metastatic pattern. A case of such a tumor is described here.

Child, Preschool↗